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Bone formation is impaired in a model of type 1 diabetes
Kathryn M Thrailkill1, Lichu Liu, Elizabeth C Wahl
1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. thrailkillkathrynm@uams.edu
Abstract:
The effects of type 1 diabetes on de novo bone formation during tibial distraction osteogenesis (DO) and on intact trabecular and cortical bone were studied using nonobese diabetic (NOD) mice and comparably aged nondiabetic NOD mice. Diabetic mice received treatment with insulin, vehicle, or no treatment during a 14-day DO procedure. Distracted tibiae were analyzed radiographically, histologically, and by microcomputed tomography (microCT). Contralateral tibiae were analyzed using microCT. Serum levels of insulin, osteocalcin, and cross-linked C-telopeptide of type I collagen were measured. Total new bone in the DO gap was reduced histologically (P < or = 0.001) and radiographically (P < or = 0.05) in diabetic mice compared with nondiabetic mice but preserved by insulin treatment. Serum osteocalcin concentrations were also reduced in diabetic mice (P < or = 0.001) and normalized with insulin treatment. Evaluation of the contralateral tibiae by microCT and mechanical testing demonstrated reductions in trabecular bone volume and thickness, cortical thickness, cortical strength, and an increase in endosteal perimeter in diabetic animals, which were prevented by insulin treatment. These studies demonstrate that bone formation during DO is impaired in a model of type 1 diabetes and preserved by systemic insulin administration.
Insights
Type 1 diabetes impairs new bone formation during distraction osteogenesis (DO) and reduces bone quality. Insulin treatment preserved bone formation and quality in diabetic mice.
Area of Science:
- Orthopedics
- Endocrinology
- Diabetology
Background:
- Type 1 diabetes (T1D) affects bone metabolism.
- Distraction osteogenesis (DO) is a surgical technique for bone lengthening.
- The impact of T1D on DO is not fully understood.
Purpose of the Study:
- To investigate the effects of T1D on de novo bone formation during tibial DO.
- To assess the impact of T1D on intact trabecular and cortical bone.
- To determine if insulin treatment can mitigate these effects.
Main Methods:
- Nonobese diabetic (NOD) mice and age-matched nondiabetic NOD mice were used.
- Diabetic mice underwent a 14-day tibial DO procedure with insulin, vehicle, or no treatment.
- Bone formation was analyzed using radiography, histology, and microcomputed tomography (microCT).
- Contralateral tibiae were analyzed using microCT and mechanical testing.
- Serum markers of bone turnover were measured.
Main Results:
- Diabetic mice showed reduced new bone formation in the DO gap (histology & radiography) compared to nondiabetic mice.
- Insulin treatment preserved new bone formation and normalized osteocalcin levels in diabetic mice.
- MicroCT and mechanical testing revealed reduced trabecular and cortical bone quality in diabetic mice.
- Insulin treatment prevented the decline in bone quality in diabetic mice.
Conclusions:
- Type 1 diabetes significantly impairs de novo bone formation during distraction osteogenesis.
- Type 1 diabetes negatively affects both trabecular and cortical bone quality.
- Systemic insulin administration can preserve bone formation and quality in the context of type 1 diabetes and DO.
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